Chem. respiratory allergens pose a significant human health hazard for many industries, yet there are currently no approved test methods to identify respiratory sensitizers. Attempts to model the processes of sensitization and elicitation in response to exposure to low mol. weight chem. allergens in animals have been unsuccessful, potentially due to insurmountable interspecies differences in the respiratory tract and/or immune system. However, the use of Adverse Outcome Pathways (AOPs) provide an avenue to establish novel approaches that can accurately identify human respiratory sensitization hazards using chem. characterization and in vitro activity profiles. An AOP describes the etiol. of a disease, disorder, or other adverse outcome (AO) as it develops from exposure to a stressor. In order to assist method developers and regulators understanding of how perturbations can be used to infer relative risks and hazards for human health, the etiol. of the AO is separated into key events corresponding to measurable perturbations, starting from the first mol. interaction with the stressor, termed the Mol. Initiating Event. In this way, AOPs are used to map physiol. relevant stages in the mechanism of toxicity to available, or potential, bioassays and test methods that measure key events upstream of the adverse outcome. These assays can then be used, often in combination, to inform on the hazards associated with chem. stressors, such as reactive electrophiles. In recent years, a variety of efforts to characterize the MIE for skin and/or respiratory sensitizers have been developed. For sensitization, protein binding is well understood to be necessary for low mol. weight chems. to induce immune responses, but much remains to be understood regarding the specific amino acid(s) and/or protein(s) that are involved in dermal and/or respiratory sensitization. To establish the most relevant evidence for human hazard identification, we have used the information on the essentiality of key events to perform a retrospective literature evaluation to identify a list of clin. respiratory sensitizers. This output will be incorporated with other available data in a weight-of-evidence approach to establish a reference chem. list of respiratory sensitizers, irritants, and non-sensitizers to use as the basis for evaluating the accuracy of test methods that characterize the MIE.